This application addresses Broad challenge area (05) Comparative Effectiveness Research and specific Challenge 05-HL-101* Treatment of Atrial Fibrillation. Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting over 2.5 million Americans at a cost of over 7 billion dollars per year to Medicare alone. Importantly, 15% of all strokes are attributed to atrial fibrillation with the atrial appendage implicated as the likely source of emboli in these patients. Literature in recent years has shown atrial fibrillation is often initiated by ectopic foci in the pulmonary veins and accordingly, there has been an explosion of catheter- based and minimally invasive surgical approaches to isolate the pulmonary vein "triggers" and ablate foci in the left atrium responsible for AF. There is some evidence that the minimally invasive surgical approach has greater primary efficacy than the catheter-based approaches and offers an added advantage in that it allows ligation of the atrial appendage -- the predominant source of emboli causing stroke in AF. Patients with strokes and AF have a 10% risk of recurrent stroke even with optimal medical management that includes anticoagulation and rate control. This application specifically addresses stroke patients with AF by comparing optimal medical therapy with a novel surgical ablative procedure that restores sinus rhythm and ligates the atrial appendage. This project includes several important outcome variables to gauge the feasibility of a larger scale multi-center clinical trial including: quality of life assessment;MRI imaging of the brain at baseline and 6 months and rigorous follow-up for recurrent stroke, bleeding and other adverse events. This protocol is unique in that it incorporates continuous remote 7 day telemetry to identify the true percentage of time patients are in atrial fibrillation (their "atrial fibrillation burden") as previous studies of AF intervention have relied on patient reported symptoms, EKGs from clinic visits or intermittent telephone follow-up. Importantly, AF can be asymptomatic but the risk for stroke is the same regardless of symptoms. This study also benefits from our center's experience in examining the quality of life patients with AF and their patient perceived success in a previous study of implantable atrial defibrillators. The University of Florida offers an ideal collaborative environment for this project with an experienced team of investigators including: a cardiothoracic surgeon with extensive clinical trial experience, a neurologist who is director of The University of Florida stroke center;the chief of electrophysiology at The University of Florida with years of ablation experience;a neuroradiologist who has previously worked on a clinical trial examining MRIs after bypass surgery and an experienced neuropsychologist with expertise in post cardiac surgery outcome and cerebrovascular disease. The current application is an ideal response to NIH Challenge 05-HL-101* treatment of atrial fibrillation because it presents an opportunity to compare the effectiveness of a novel minimally invasive surgical therapy for atrial fibrillation to current medical management. If minimally invasive surgical atrial ablation is found to be superior to medical therapy it could benefit not only stroke patients with AF -- but the entire population of 2.5 million Americans currently suffering from AF. The University of Florida contributes substantially to the local and regional economy. In 2008, UF created 2,525 jobs and recent studies have shown that UF contributes nearly $6 billion annually to Florida's economy. The university employs about 34,000 people directly on its main campus and via UF organizations, such as the Institute of Food and Agricultural Sciences, is responsible for the creation of 74,894 jobs statewide. The current application will create or retain 7 jobs with the potential to create many more if pilot data from this project is translated into a multicenter clinical trial. PUBLIC HEALTH RELEVANCE: Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting over 2.5 million Americans at a cost of over 7 billion dollars per year to Medicare alone. Importantly, 15% of all strokes are attributed to atrial fibrillation with the atrial appendage implicated as the likely source of emboli in these patients. This application specifically addresses stroke patients with AF by comparing optimal medical therapy with a novel surgical ablative procedure that restores sinus rhythm and ligates the atrial appendage.